A new vaccine for Kovid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam may change how the world fights the epidemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to produce more potent antibodies than the current generation of vaccines. And it can be very easy to make a new vaccine.
Existing vaccines from companies such as Pfizer and Johnson & Johnson must be produced using hard-to-exit materials in specialized factories. In contrast, the new vaccine can be mass-produced in chicken eggs – the same eggs that produce billions of influenza each year in factories around the world.
If NVD-HXP-S proves to be safe and effective, flu vaccine manufacturers could potentially produce more than a billion doses a year. Low- and middle-income countries Currently struggling to get vaccines Wealthy countries may be able to build NVD-HXP-S for themselves or get it from neighbors at a lower cost.
“It’s staggering. It will be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.
First, however, clinical trials have to establish that NVD-HXP-S actually works in people. The first phase of clinical trials will end in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for vaccine prospects.
Dr. of the PATH Center for Vaccine Innovation and Access “This is a home run for safety, which has coordinated the development of NVD-HXP-S,” said Bruce Innes. “I think it’s a world-class vaccine.”
2P to the rescue
Vaccine work It is sufficient to defend against it by thoroughly familiarizing the immune system with a virus. Some vaccines contain whole viruses that have been killed; Others contain only one protein from the virus. Still others have genetic instructions that our cells can use to make viral proteins.
Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.
In the case of coronovirus, the best target for the immune system is the protein that covers its surface like a crown. Protein, known as Wedge, Latch onto cells and then allow the virus to fuse them.
But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. This is because spike proteins sometimes take the wrong shape, and signal the immune system to make the wrong antibodies.
This insight was revealed long before the Kovid-19 epidemic. In 2015, another coronovirus appeared, leading to a fatal form of pneumonia called MERS. Jason McKellan, a structural biologist, then at the Gesell School of Medicine in Dartmouth, and his colleagues determined to make a vaccine against it.
They wanted to use the spike protein as a target. But he had to agree with the fact that the spike protein is a shape-shifter. As the protein prepares for a cell to fuse, it resists in a spear for a spear more than a tulip-like shape.
Scientists have termed these two figures as pre-fusion and post-shapes of the spike. Antibodies against prefusion motifs potentiate against coronovirus, but postfusion antibodies do not harbor it.
Dr. McLennan and his colleagues used standard techniques to create the MERS vaccine, but ended up with too many postfusion spikes, which were useless for their purposes. They then found a way to keep the protein locked into a prefabricated shape like a tulip. All they had to do was convert two of the more than 1,000 building blocks in the protein into a compound called proline.
The resulting spike – called 2P, for two new proline molecules – had a higher probability of assuming the desired tulip shape. Researchers inject 2P spikes into mice And found that animals can fight MERS coronavirus infection easily.
The team filed a patent for their modified spike, but the world took very little notice of the invention. MERS, although fatal, is not very contagious and proves to be a relatively minor threat; Less than 1,000 people have died from MERS since humans first emerged.
But at the end of 2019, a new coronavirus, SARS-CoV-2, emerged and devastated the world. Dr. McClain and his colleagues got into action, making a 2P spike unique to SARS-CoV-2. In a few days, Modern used that information to design the vaccine for the Kovid-19; It consisted of a genetic molecule called RNA with instructions for making a 2P spike.
Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and beginning clinical trials. In the United States all three vaccines – hitherto authorized from Johnson & Johnson, Moderna and Pfizer-BioNotech – use the 2P spike.
Other vaccine manufacturers are also using it. Novaxax Clinical trials have found strong results with the 2P spike and are expected to apply to the Food and Drug Administration for Emergency Use Authority over the next few weeks. Sanofi 2P is also testing the spike vaccine and is expected to conclude clinical trials later this year.
Two offers are good; Six is better
Dr. McLean’s ability to find lifelong clues in the structure of proteins has earned him deep acclaim in the vaccine world. “It’s a talented person,” said Harry Cleanthus, a senior program officer at the Bill & Melinda Gates Foundation. “They should be proud of this huge thing that they have done for humanity.”
But once Dr. McLennan and his colleagues handed the 2P spike to the vaccine makers, so they resorted to protein for a closer look. If the exchange of just two props led to an improvement in a vaccine, additional tweaks could certainly make it even better.
“It makes sense to try to get a better vaccine,” Drs. McLennan, now an associate professor at the University of Texas at Austin.
In March, he joined forces with two Texas biologists, Ilya Finkelstein and Jennifer Maynard. His three laboratories created 100 new spikes, each with a converted building block. With funding from the Gates Foundation, they tested each one and then added changes to the new spikes. Eventually, he created a single protein that fulfilled his aspirations.
The winner incorporated two previews into the 2P spike, along with four additional proteins found elsewhere in the protein. Dr. McLennan calls for new spike HexaPro, In honor of its six total episodes.
The team found that the structure of Hexpro was more stable than that of 2P. It was also flexible, better able to withstand heat and harmful chemicals. Dr. McLennan hoped that its rude design would make it powerful in vaccines.
Dr. McLennan also hoped that hexapro-based vaccines would reach more of the world – especially low- and middle-income countries, which have received only a fraction of the total distribution of first-wave vaccines so far.
Dr. “The portion of the vaccines they have received so far is terrific,” McLennan said.
To that end, the University of Texas established a licensing regime for Hexapro, which allows 80 low- and middle-income countries to use protein in their vaccines without paying royalties.
Meanwhile, PATH has Drs. Ines and his colleagues were looking for a way to increase production of Kovid-19 vaccines. They wanted a vaccine that less wealthy nations could create on their own.
With a little help from eggs
The first wave of authorized Kovid-19 vaccines requires specialized, expensive materials. For example, Modern’s RNA-based vaccine requires genetic building blocks called nucleotides, as well as custom-made fatty acids to form a bubble around them. Those materials should be collected in vaccines in purpose-built factories.
The way influenza vaccines are produced is a study to the contrary. Many countries have huge factories for making cheap flu shots, in which influenza virus is injected into chicken eggs. Eggs produce an abundance of new copies of the virus. Factory workers then remove the virus, weaken or kill them, and then inject them into vaccines.
The PATH team wondered if scientists could make a Kovid-19 vaccine that could be cheaply grown in chicken eggs. In this way, the same factories that make flu shots can also produce Kovid-19 shots.
In New York, a team of scientists from the Icon School of Medicine at Mount Sinai knew to use a bird virus called Newcastle disease virus that is harmless in humans.
For years, scientists had Newcastle disease experiment with virus To make vaccines for a range of diseases. For example, to develop the Ebola vaccine, researchers added an Ebola gene to their group of genes for the Newcastle disease virus.
The scientists then inserted the engineer’s virus into the chicken egg. Because it is a bird virus, it multiplies quickly in eggs. Researchers eliminated the Newcastle disease virus coated with Ebola protein.
At Mount Sinai, researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When he got Dr. When asked about the new hexopro version of McLeanan, he said that in the Newcastle disease virus. The virus was loaded with spike proteins, many of which had the desired proliferation size. In a node for both the Newcastle disease virus and the hexopro spike, they called it NDV-HXP-S.
PATH arranged thousands of doses of NDV-HXP-S at a Vietnamese factory that commonly produces influenza vaccines in chicken eggs. In October, the factory sent vaccines to New York for testing. Researchers at Mount Sinai found that NDV-HXP-S provided powerful protection in mice and hamsters.
“, I can honestly say that I can protect every hamster, every mouse in the world against SARS-CoV-2,” research leader Dr. Peter Palasi said. “But the jury is still out about what she does in humans.”
The vaccine’s ability brought an additional benefit: researchers needed fewer viruses for an effective dose. Five to 10 doses of NDV-HXP-S can be excreted in a single egg compared to one or two doses of influenza vaccines.
“We’re very excited about this, because we think it’s a way to make a cheaper vaccine,” Dr. Palese said.
PATH paired the Mount Sinai team with influenza vaccine manufacturers. On March 15, Vietnam’s Institute of Vaccines and Medical Biology Announced Initiation of clinical trials of NDV-HXP-S. A week later, Thailand’s government pharmaceutical organization followed suit. On 26 March, the Butanan Institute of Brazil said It will also demand authorization to begin its own clinical trials of NDV-HXP-S.
Meanwhile, the Mount Sinai team also has Licensed Vaccine as an intranasal spray to Mexican vaccine manufacturer AV-MX. The company will begin clinical trials to see if the vaccine is even more potent in that form.
For the countries involved, vaccines looked likely to be made entirely on their own. “The vaccine is produced by the Thai people for the Thai people,” Thailand’s Health Minister, Antin Churnavirakul, said in the announcement in Bangkok.
In Brazil, the Butanon Institute trumpeted its version of the NDV-HXP-S as the “Brazilian Vaccine”, which was “fully produced in Brazil, without import.”
Ms. Taylor was a sympathizer of the Duke Global Health Innovation Center. “I could understand why that would really be such an attractive prospect,” she said. “They have been at the mercy of the global supply chain.”
Madhavi Sundar, an intellectual property expert at Georgetown Law School, warned that NDV-HXP-S would not immediately help countries like Brazil as they were struggling with the current wave of Kovid-19 infection. “We’re not talking 16 billion doses in 2020,” she said.
Instead, the strategy will be important for long-term production – not only for Kovid-19 but also for other future epidemics. “It sounds super promising,” he said.
Meanwhile, Drs. McLennan has returned to the molecular drawing board to try to create a third version of his spike that is even better than HexPro.
“There is really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you have to say, ‘This is the next generation’.